Recent evidence suggests that enhancing antibodies (or "factors") are formed during a wide variety of immunological responses, including those occurring in cancer patients, during pregnancy, and in allograft acceptance. Little is known of the specificity or immunochemical nature of serum blocking factors found in these situations nor of conditions which favor their induction or termination. The objectives of the proposed research are: 1) to characterize the specificity and immunochemical nature of enhancing factors, 2) to determine whether serum blocking factors present in these allo-immune states are similar and 3) to study, in a mouse model, conditions favoring the development of such factors by exploring the effects of pregnancy, gestational hormones, the sources and maturity of the immunizing tissues, and the mode of presentation of the allo-antigens to the host. The objectives will be approached initially by absorption of human blocking plasmas obtained from multiparous women with platelets and leukocytes from their husbands and reexamining their abilities to block in mixed leukocyte culture. Further, attempts will be made to characterize blocking factors by ion-exchange, gel filtration and affinity chromatography of these plasmas and of supernatants from mixed leukocyte cultures conducted in medium supplemented with blocking plasmas. The effects of gestational hormones on the induction of enhancing antibodies will be examined by treating mice with various such hormones before and after immunization with lyophilized spleen cells and assaying for enhancing factors by abrogation of mixed leukocyte responses, avoidance of G-V-H in parental to F sub 1 hybrid immunocompetent cell transfers, and prolongation of survival of tumors syngeneic to the donors of the immunizing cells. Various fetal and adult tissues will be compared and the intravenous, intraperitoneal, intradermal, and intramuscular routes examined for their possible influences on the induction of blocking factors. Elucidation of the nature and specificity of these factors should hasten the application of enhancement of clinical organ and tissue transplantation. Moreover, with knowledge of conditions leading to the induction and persistence of blocking antibodies, it should be possible to select conditions which favor their termination in cancer.